European Network for Patient Safety and Quality of Care: PaSQ / La red de la Unión Europea para la Seguridad del Paciente y la Calidad Asistencial: PasQ

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Anti-heart and anti-intercalated disk autoantibodies: evidence for autoimmunity in idiopathic recurrent acute pericarditis.

BACKGROUND: Idiopathic recurrent acute pericarditis (IRAP) is a rare disease of suspected, yet unproved, immune-mediated origin. The finding of serum heart-specific autoantibodies in IRAP would strengthen the autoimmune hypothesis and provide aetiology-specific non-invasive biomarkers. Objective To assess frequency of serum anti-heart (AHA), anti-intercalated-disk (AIDA) and non-cardiac-specific autoantibodies and their clinical and instrumental correlates in patients with IRAP. Patients 40 consecutive patients with IRAP, 25 male, aged 37+/-16 years, representing a large single-centre cohort collected at a referral centre over a long time period (median 5 years, range 1-22 years). Control groups included patients with non-inflammatory cardiac disease (NICD) (n=160), ischaemic heart failure (n=141) and normal subjects (n=270). METHODS: AHA (organ-specific, cross-reactive 1 and 2 types) and AIDA were detected in serum samples from patients, at last follow-up, and control subjects by indirect immunofluorescence (IIF) on human myocardium and skeletal muscle. Non-cardiac-specific autoantibodies were detected by IIF, and anti-Ro/SSA, anti-La/SSB by ELISA. RESULTS: The frequencies of cross-reactive 1 AHA and of AIDA were higher (50%; 25%) in IRAP than in NICD (4%; 4%), ischaemic (1%; 2%) or normal subjects (3%; 0%) (p=0.0001). AHA and/or AIDA were found in 67.5% patients with IRAP. Of the non-cardiac-specific antibodies, only antinuclear autoantibodies at titre > or =1/160 were more common in IRAP (5%) versus normal (0.5%, p<0.04). AIDA in IRAP were associated with a higher number of recurrences (p=0.01) and hospitalisations (p=0.0001), high titre (1/80 or higher) AHA with a higher number of recurrences (p=0.02). CONCLUSIONS: The detection of AHA and of AIDA supports the involvement of autoimmunity in the majority of patients with IRAP.

Autoimmune myocarditis and dilated cardiomyopathy: focus on cardiac autoantibodies.

Criteria of organ-specific autoimmunity are fulfilled in a subset of patients with myocarditis/dilated cardiomyopathy (DCM). In particular, circulating heart-reactive autoantibodies are found in patients and symptom-free relatives. These autoantibodies are directed against multiple antigens, some of which are expressed in the heart (organ-specific), others in heart and some skeletal muscle fibres (partially-heart specific) or in heart and skeletal muscle (muscle-specific). Distinct autoantibodies have different frequency in disease and normal controls. Different techniques detect one or more antibodies, thus they cannot be used interchangeably for screening. It is unknown whether the same patients produce more antibodies or different patient groups develop autoimmunity to distinct antigens. IgG antibodies, shown to be cardiac and disease-specific for myocarditis/DCM, can be used as autoimmune markers for identifying patients in whom immunosuppression may be beneficial and relatives at risk. Some autoantibodies may also have a functional role, but further work is needed.

Acute effects of the oral administration of midodrine, an alpha-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites.

The effects of the acute administration of arterial vasoconstrictors on renal plasma flow (RPF) and urinary sodium excretion (UNaV) in cirrhotic patients with ascites with or without hepatorenal syndrome (HRS) are still controversial. As a consequence, vasoconstrictors are not actually used in the treatment of renal sodium retention or HRS in these patients, regardless of the several lines of evidence suggesting that these renal functional abnormalities are related to a marked arterial vasodilation. The lack of an orally available effective arterial vasoconstrictor probably represents a further reason for this omission. Consequently, the present study was made to evaluate the acute effects of the oral administration of midodrine, an orally available -mimetic drug, on systemic and renal hemodynamics and on UNaV in cirrhotic patients with ascites. Mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), systemic vascular resistance (SVR), left forearm blood flow (LFBF), left leg blood flow (LLBF), RPF, glomerular filtration rate (GFR), UNaV, plasma renin activity (PRA), plasma concentration of antidiuretic hormone (ADH), and the serum levels of nitrite and nitrate (NOx) were evaluated in 25 cirrhotic patients with ascites (17 without HRS and 8 with type 2 HRS) before and during the 6 hours following the oral administration of 15 mg of midodrine. During the first 3 hours after the drug administration, a significant increase in MAP (89.6 +/- 1.7 vs. 81.80 +/- 1.3 mm Hg; P < .0001) and SVR (1, 313.9 +/- 44.4 vs. 1,121.2 +/- 60.1 dyn . sec . cm-5; P < .0001) accompanied by a decrease in HR (69 +/- 2 vs. 77 +/- 3 bpm; P < .005) and CI (2,932.7 +/- 131.4 vs. 3,152.5 +/- 131.4 mL . min-1 . m2 BSA; P < .0025) was observed in patients without HRS. No change was observed in LFBF and LLBF. The improvement in systemic hemodynamics, which was also maintained during the the 3- to 6-hour period after midodrine administration, was accompanied by a significant increase in RPF (541.5 +/- 43.1 vs. 385.7 +/- 39.9 mL . min-1; P < .005), GFR (93.1 +/- 6.5 vs. 77.0 +/- 6.7 mL . min-1; P < .025), and UNaV (92.7 +/- 16.4 vs. 72.2 +/- 10.7 microEq . min-1; P < .025). In addition, a decrease in PRA (5.33 +/- 1.47 vs. 7.74 +/- 2.17 ng . mL-1 . h; P < .05), ADH (1.4 +/- 0.2 vs. 1.7 +/- 0.2 pg . mL-1; P < .05), and NOx (33.4 +/- 5.0 vs. 49.3 +/- 7.3 micromol-1; P < .05) was found. In patients with HRS, the effects of the drug on the systemic hemodynamics was smaller and shorter. Accordingly, regardless of a significant decrease in PRA (15.87 +/- 3.70 vs. 20.70 +/- 4.82 ng . mL-1 . h; P < .0025) in patients with HRS, no significant improvement was observed in RPF, GFR, or UNaV. In conclusion, the acute oral administration of midodrine is associated with a significant improvement in systemic hemodynamics in nonazotemic cirrhotic patients with ascites. As a result, renal perfusion and UNaV also improve in these patients. By contrast, midodrine only slightly improves systemic hemodynamics in patients with type 2 HRS, with no effect on renal hemodynamics and renal function.

Pharmaceutical services in the United States Army.

The status of pharmaceutical services in the United States Army is described. The Army Medical Department (AMEDD) has 157 commissioned pharmacy officers and 399 civilian pharmacists working in the United States and overseas. Pharmaceutical services are provided from fixed medical treatment facilities on Army installations and, during war and other field operations, field hospitals. Reductions in personnel and facility closures have helped align the AMEDD with the size of the Army's activeduty force, but there has been only a 15% reduction in the number of eligible beneficiaries. Measures such as the interservice TRICARE program have been implemented to help meet the continued high demand for pharmaceutical services cost-effectively. Army pharmacy is similar to civilian pharmacy, except that Army hospitals often include high-volume outpatient pharmacies not usually found in civilian institutions. Pharmacists are being given direct patient care roles on multidisciplinary teams. Army pharmacists participate in field exercises so that they will be prepared to provide services under combat conditions. The AMEDD trains its own pharmacy technicians in a highly structured 18-week course. A triservice Pharmacoeconomic Center (PEC) has been established with the goal of providing prescribers with the tools for making cost-effective decisions about drug therapy, including a formulary. Army pharmacy officers have broad opportunities to further their education and training. In preparing for the next century, Army pharmacists need to continue to prove their value to the AMEDD, the Army, and the Department of Defense.

Determination of inulin in plasma and urine by reversed-phase high-performance liquid chromatography.

We report a new HPLC procedure for measuring inulin in plasma and urine. Samples after dilution are boiled in mild acidic conditions and then analyzed on a C18 column. Solvent system A is 3.2 mM HCl, pH 2.5, and B is acetonitrile-3.2 mM HCl (60:40, v/v), pH 2.5. The separation is carried out in 8 min with a flow-rate of 1.0 ml/min and the absorbance monitored at 280 nm. The relationship between inulin and the recorded peak area is linear from 0.2 to 3.2 mg/ml with a correlation coefficient of 0.999 for plasma and 0.999 for urine. Within-run precision, measured at three inulin concentrations, ranged from 0.9 to 1.7% in plasma and from 0.8 to 1.2% in urine. Between-run precision varied in plasma from 2.7 to 3.2% and in urine from 3.0 to 3.3%. Analytical recovery ranged from 102 to 107% in plasma and from 101 to 105% in urine, respectively. The method is sensitive, selective and only 30-microliters samples are required. Therefore, it could be used to evaluate the glomerular filtration rate even in small babies and to perform studies in animals.

Determination of 8-methoxypsoralen in plasma by gas chromatography-mass spectrometry using selected-ion monitoring.

A sensitive and accurate assay was developed for the measurement of 8-methoxypsoralen in plasma using electron-impact positive-ion mass fragmentography. 4,5,8-Trimethylpsoralen was used as an internal standard. Sample preparation consisted of a two-step liquid phase extraction using acetonitrile and methylene chloride. The calibration curve showed a linear relationship between the peak areas of 8-methoxypsoralen and 4,5,8-trimethylpsoralen over a wide range of 8-methoxypsoralen concentrations (1-500 ng/ml). With-in- and between-run precisions, measured at five different drug concentrations, varied from 0.82 to 1.41% and from 0.82 to 1.86%, respectively.